Definition:
Tay-Sachs disease is a fatal genetic disorder that causes progressive destruction of the central nervous system in children.

Tay-Sachs disease is caused by the absence of a vital enzyme called hexosaminidase A (Hex-A). Without Hex-A, a fatty substance or lipid called GM2 ganglioside accumulates abnormally in cells, especially in the nerve cells of the brain. Gangliosides need to be biodegraded rapidly in early life as the brain develops. This ongoing accumulation causes progressive damage to the cells.

In the general population, about one out of every 320,000 babies born has Tay-Sachs disease and approximately one in 30 Ashkenazi Jews is a carrier of the gene that causes this disease. Even though there is a high incidence of this disease among people of Eastern European and Askhenazi Jewish descent, Tay-Sachs disease has been reported in children of virtually all ethnic, racial, and religious populations.  French Canadians of the eastern St. Lawrence River Valley area of Quebec, Cajuns from Louisiana, and the Old Order Amish in Pennsylvania have been found to carry the mutation with frequencies equal to or even greater than those seen in the Ashkenazi Jewish population.

Because of the increased occurrence of the disease among Ashkenazi Jews, along with the availability of genetic counseling and prenatal diagnosis, population screening was initiated in 1970 for Jewish individuals of reproductive age and is recommended in published guidelines of the American College of Obstetrics and Gynecology and the American College of Medical Genetics [Kaback et al 1993]. This screening program educates couples in which both partners are carriers, regarding their status and the risks associated with giving birth to affected children. Genetic counseling and the option of prenatal testing allows such families the choice to bring to term only those pregnancies in which the fetus is unaffected. This program has reduced the incidence of Tay-Sachs among the Ashkenazi population by more than 90 percent.

Tay-Sachs disease has a continuum of severity based on the amount of residual Hexosaminidase A activity present in the cells.  The amount of residual activity depends on the particular mutation in the Tay-Sachs gene. This dynamic is expressed through two variations of Tay-Sachs disease. These two variants are Juvenile Hexosaminidase A deficiency and Chronic Hexosaminidase A deficiency. 

Symptoms:
A baby with Tay-Sachs disease appears normal at birth and seems to develop normally until about six months of age. The first signs can vary and are evident at different ages in affected children.  Initially, development slows, there is a loss of peripheral vision, and the affected child exhibits an abnormal, startled response to noise.  By about two years of age, most affected children experience recurrent seizures and diminishing mental function. The affected child regresses gradually, loses skills one by one, and is eventually unable to crawl, turn over, sit or reach out. Other symptoms include increasing loss of coordination, progressive inability to swallow and breathing difficulties. Eventually, the affected child becomes blind, mentally retarded, paralyzed, and unresponsive to his or her environment.

Inheritance Pattern:
Tay-Sachs disease is an autosomal recessive disorder.

Diagnosis and Testing:
Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures the enzymatic activity of beta-hexosaminidase A.  Both parents must carry the mutated gene to have an affected child. In these instances, there is a 25% chance with each pregnancy that the child will be affected with Tay-Sachs disease. Prenatal diagnosis is also available if the pregnant mother knows that both she and the father of her unborn child carry the gene mutation.

Life Expectancy:
Life expectancy for Tay-Sachs disease is four years of age or younger. The cause of death is typically pneumonia.

Treatment:
Currently, there is no cure or effective treatment for Tay-Sachs disease. Anticonvulsant medicine can help to control seizures. Other treatment options include adequate nutrition and hydration as well as techniques to keep the airway open.  A feeding tube may also be necessary for some children.

Enzyme replacement therapy using a synthetic version of the enzyme Hex-A, which is missing in babies with Tay-Sachs disease, has been explored. Although this approach is promising, scientists face obstacles since the disease affects brain cells protected by the blood-brain barrier. Enzymes like Hex-A are blocked from entering the brain from the blood.

Bone marrow transplantation has been attempted, but to date has not been successful in reversing or slowing damage to the central nervous system in babies with TSD.   The National Institute of Neurological Disorders and Stroke, which is part of the National Institutes of Health, is conducting research to find additional therapies and treatments for this disease. There is hope that other treatments such as gene therapy targeted to cells in the central nervous system and/or the introduction of functional neural stem cells into the brains of affected children will help to reverse the symptoms of this disorder.

Patient Groups:
National Tay-Sachs & Allied Diseases Association
2001 Beacon Street, Suite 204
Boston, MA 02135
www.ntsad.org
tel: (800) 906-8723
fax: (617) 277-0134
Sue R. Kahn, Executive Director
info@ntsad.org